Scintigraphy using monoclonal antibodies has been suggested as a possible adjunct to conventional staging techniques for the routine staging and diagnosis of Langerhans cell histiocytosis. In this study we have developed a model for Langerhans cell histiocytosis comprising a CD1a-positive subcutaneous xenograft in the flanks of nude (nu/nu) mice. The anti-CD1a murine monoclonal antibody NA1/34 was investigated for its potential both as an imaging and as a therapeutic targeting agent in this model. Biodistribution with NA1/34 compared with irrelevant isotype-matched monoclonal antibody demonstrated specific accumulation within the xenografts of 10.0%id per g (percentage injected dose per gram) and 3.3%id per g at 48 h postinjection, respectively. NA1/34 displayed no specific accumulation to CD1a-negative xenografts. F(ab')2 fragments of NA1/34 displayed a faster clearance time of 19.6 h compared with the intact antibody, 122.4 h, resulting in a more rapid maximum xenograft uptake time of 5 h compared with 48 h postinjection for the intact antibody. Although the overall xenograft/tissue ratio for the F(ab')2 was at no time greater than that for the intact antibody, the F(ab')2 did display dramatically greater xenograft/blood ratios, reaching 19:1 at 120 h postinjection Xenograft regression using single doses of 350 microCi and 500 microCi 131I-labeled NA1/34 significantly (p < 0.001) delayed xenograft progression compared with control nonirradiated xenografts, with average delays of 3.2 and 5.7 times the control, respectively. This study suggests that the anti-CD1a monoclonal antibody, NA1/34, offers advantages in the prognosis and staging of Langerhans cell histiocytosis, in a human setting. We discuss the advantages of radioimmunoscintigraphy over conventional differential diagnostic techniques. The potential for the future radioimmunotherapy of Langerhans cell histiocytosis is also discussed.